We have continued our efforts to identify and characterize frequent genetic changes associated with primary human breast tumor DNAs. In 20% of the tumor DNAs (n=56), heterozygosity of multiple loci on chromosome 11p was lost. The somatic loss of these sequences have a significant correlation with histopathological grade III tumor (P less than .006), estrogen and progesterone receptor negative tumors (P less than .02 and P less than .002, respectively) and patients which develop distalmetastasis (P less than .05). Our data suggests that the most frequently deleted region lies between the beta Globin and PTH loci. In situ RNA:RNA hybridization on frozen sections of primary breast and colon carcinomas was used to examine cmyc and cHras-1 expression. In the breast carcinomas high levels of cmyc RNA expression; with few exceptions, correlates with amplification of the gene. The expression of cmyc and cHras-1 in colon carcinomas is aberrantly regulated in several cases. Their expression is not a function of the proliferative capacity of the tumor. In addition no genetic alterations of these genes could be detected which explain the patterns of expression observed.